Cs + ADC in rat brain decreases markedly at death

Goodman, James A.; Ackerman, Joseph J. H.; Neil, Jeffrey J.

doi:10.1002/mrm.21418

Cited by 20 publications

(20 citation statements)

References 34 publications

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“…In the current model, an amplitude of 0.6 and an initial radius of 1 μm resulted in an intracellular MD decrease of 79%. This agrees with the 76% decrease of intracellular MD measured in vivo after global ischemia (17), but it should be noted that there are significant limitations in the direct comparison between the two results. Specifically, the current model does not account for diffusion within cell bodies, axon terminals, and glial cells, including myelin, that could influence the measurements.…”

Section: Discussionsupporting

confidence: 87%

“…We also purposely neglected other structures composing CNS tissues, including neuronal cell bodies, glial cells, and subcellular organelles and cytoskeletal elements that contribute in unique ways to the diffusion properties of normal and injured tissues. Nonetheless, compared with models that implicate changes in bulk-water compartmentalization or extracellular tortuosity for the decrease in MD, the finding that these changes are dominated by intracellular diffusion is largely supported by experimental studies (17,45). Similarly, the beading model of decreased intracellular diffusion is well-suited to validation using MR-based or microscopy-based techniques.…”

Section: Discussionmentioning

confidence: 99%

“…In normal neurites, water mobility is highly restricted by the cell membrane perpendicular to the main axis, whereas water molecules diffusing along the main axis of the neurite encounter few barriers on the timescale of diffusion MRI measurements (16). Recently, it was shown in a model of global ischemia that diffusion within the intracellular space decreases to one-fourth of its preischemic value (17). Therefore, because cell membranes present the greatest hindrance to the diffusion of water molecules in biological tissues (18), we further hypothesize that the ADC decrease is specifically caused by a reduction in the mobility of intracellular water along the main axis of each neurite.…”

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confidence: 99%

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Neurite beading is sufficient to decrease the apparent diffusion coefficient after ischemic stroke

Budde¹,

Frank

2010

Proc. Natl. Acad. Sci. U.S.A.

211

193

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Diffusion-weighted MRI (DWI) is a sensitive and reliable marker of cerebral ischemia. Within minutes of an ischemic event in the brain, the microscopic motion of water molecules measured with DWI, termed the apparent diffusion coefficient (ADC), decreases within the infarcted region. However, although the change is related to cell swelling, the precise pathological mechanism remains elusive. We show that focal enlargement and constriction, or beading, in axons and dendrites are sufficient to substantially decrease ADC. We first derived a biophysical model of neurite beading, and we show that the beaded morphology allows a larger volume to be encompassed within an equivalent surface area and is, therefore, a consequence of osmotic imbalance after ischemia. The DWI experiment simulated within the model revealed that intracellular ADC decreased by 79% in beaded neurites compared with the unbeaded form. To validate the model experimentally, excised rat sciatic nerves were subjected to stretching, which induced beading but did not cause a bulk shift of water into the axon (i.e., swelling). Beading-induced changes in cell-membrane morphology were sufficient to significantly hinder water mobility and thereby decrease ADC, and the experimental measurements were in excellent agreement with the simulated values. This is a demonstration that neurite beading accurately captures the diffusion changes measured in vivo. The results significantly advance the specificity of DWI in ischemia and other acute neurological injuries and will greatly aid the development of treatment strategies to monitor and repair damaged brain in both clinical and experimental settings.is an exceptionally sensitive indicator of ischemic stroke and is, therefore, an important clinical diagnostic tool. Within minutes of the stroke onset, the microscopic motion of water molecules, termed the apparent diffusion coefficient (ADC), dramatically decreases in the infarcted brain region (1). However, the underlying cause of the decrease in ADC in still unknown. The available evidence suggests that the change is intimately related to cellular swelling (2, 3), but the precise biophysical mechanism remains elusive.The CNS maintains a highly regulated ionic equilibrium, but oxygen and glucose deprivation, such as that experienced during ischemia, disrupts this delicate balance. In normally functioning neurons, the resting ionic balance across neuronal membranes is largely dependent on the transmembrane Na + /K + ATPase, which removes intracellular Na + in exchange for the entry of K + . The failure of this enzyme leads to an osmostic imbalance and swelling of the cell. It is believed that this rapid shift in water from the extracellular to the intracellular space causes ADC to decrease after ischemia, but exactly how this occurs is the subject of intense debate. Many theories have been proposed (4, 5), but none of these models has sufficiently captured both the magnitude of the measured diffusion changes and the underlying pathophysiology of injury. Unlike spheri...

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Neurite beading is sufficient to decrease the apparent diffusion coefficient after ischemic stroke

Budde¹,

Frank

2010

Proc. Natl. Acad. Sci. U.S.A.

211

193

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“…Non-proton probes have been used to selectively probe either the extracellular space (sodium-based (Goodman et al, 2005)), the intracellular space (cesium-based (Goodman et al, 2008)) or each of them separately (fluorine-based (Duong et al, 1998)). The diffusivity of extracellular proton-based agents such as mannitol, phenylphosphonate and polyethylene glycols has also been investigated using diffusion spectroscopy (Duong et al, 2001).…”

Section: Validating Diffusion Modelsmentioning

confidence: 99%

“…. Compartment-specific tracer studies have indicated that the intracellular and extracellular compartments exhibit similar decreases in diffusion (Duong et al, 1998; Silva et al, 2002), while others have shown that intracellular diffusivity decreases substantially while the extracellular diffusivity experiences a somewhat lesser decrease (Goodman et al, 2008). The extracellular decrease is consistent with a reduction in the extracellular space and increase in tortuosity that leads to decreased diffusivity in that compartment (Latour et al, 1994), while the intracellular decrease is consistent with neurite beading (Baron et al, 2015; Budde and Frank, 2010).…”

Section: Parameter Choice In the Injured And Diseased White Mattermentioning

confidence: 99%

Design and Validation of Diffusion MRI Models of White Matter

2017

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Diffusion MRI is arguably the method of choice for characterizing white matter microstructure in vivo. Over the typical duration of diffusion encoding, the displacement of water molecules is conveniently on a length scale similar to that of the underlying cellular structures. Moreover, water molecules in white matter are largely compartmentalized which enables biologically-inspired compartmental diffusion models to characterize and quantify the true biological microstructure. A plethora of white matter models have been proposed. However, overparameterization and mathematical fitting complications encourage the introduction of simplifying assumptions that vary between different approaches. These choices impact the quantitative estimation of model parameters with potential detriments to their biological accuracy and promised specificity. First, we review biophysical white matter models in use and recapitulate their underlying assumptions and realms of applicability. Second, we present up-to-date efforts to validate parameters estimated from biophysical models. Simulations and dedicated phantoms are useful in assessing the performance of models when the ground truth is known. However, the biggest challenge remains the validation of the “biological accuracy” of estimated parameters. Complementary techniques such as microscopy of fixed tissue specimens have facilitated direct comparisons of estimates of white matter fiber orientation and densities. However, validation of compartmental diffusivities remains challenging, and complementary MRI-based techniques such as alternative diffusion encodings, compartment-specific contrast agents and metabolites have been used to validate diffusion models. Finally, white matter injury and disease pose additional challenges to modeling, which are also discussed. This review aims to provide an overview of the current state of models and their validation and to stimulate further research in the field to solve the remaining open questions and converge towards consensus.

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Low‐bandwidth space/frequency component separation for quantitative imaging

Zubkov

Stait‐Gardner

Price

2016

Magnetic Reson in Chemistry

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Quantitative MRI is often used to analyse multicomponent systems. The analysis requires the contributions from different species to be isolated. Species with distinct chemical shifts can be separated by using a low acquisition bandwidth, which is easy to achieve in common quantitative imaging protocols. The bandwidth reduction leads to separation of NMR contributions from different species in the image space. This new method was implemented and tested on two multicomponent systems containing several spectrally and spatially unresolved components with both distinctly different and similar diffusion coefficients and relaxation times. Separation was achieved with routine MRI diffusion and relaxation measurement pulse sequences in a microimaging environment for water/polyethylene glycol solution and for chloroform/TMS/polyethylene glycol solution. Conventional monoexponential fitting was used to determine diffusion coefficients and relaxation times from the spectrally separated data, whereas biexponential or triexponential fitting was required in the unseparated reference experiments. In the two-component sample, the variation in the determined fast diffusing components was on the same order of magnitude for all experiments, while the variation in the slow diffusing polyethylene glycol was larger when no separation was present. The separation technique provided lower variability for all the determined diffusion coefficients and relaxation times in the three-component sample. The low-bandwidth separation method can provide separation of multicomponent systems based on the chemical shift difference between the species. The accuracy of the technique is comparable with the commonly used methods for bicomponent system analysis and surpasses those when there are more than two components in the sample. Copyright © 2016 John Wiley & Sons, Ltd.

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Cs + ADC in rat brain decreases markedly at death

Cited by 20 publications

References 34 publications

Neurite beading is sufficient to decrease the apparent diffusion coefficient after ischemic stroke

Neurite beading is sufficient to decrease the apparent diffusion coefficient after ischemic stroke

Design and Validation of Diffusion MRI Models of White Matter

Low‐bandwidth space/frequency component separation for quantitative imaging

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